"Baricitinib for Treating Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype, an International Phase II/Phase III, Randomized, Controlled Trial - TREAT-HAP Study.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 450
- 试验地点
- 24
- 主要终点
- Determine the safety (phase II), of baricitinib plus standard of care (SOC) as compared to (SOC) alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile
研究概览
简要总结
The goal of this clinical trial is to determine the safety (phase II), then efficacy (phase III) of baricitinib plus standard of care (SOC) as compared to SOC alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile.
详细描述
For both groups :
At inclusion visit :
- Verification of inclusion and non-inclusion criteria
- Patient information and signature of consent form
- Pregnancy test (urine ou blood)
- Randomization
- Clinical evaluation (cardiac frequency, saturation, tracheal secretions, PaO2/FiO2 ratio, body temperature, mechanical ventilation support)
- Collection of respiratory fluid and blood for biobank
- Liver function test (AST, ALT, bilirubin), blood white cells count and EKG
- Treatment compliance
- Concomitant medications (antimicrobial therapy and steriods)
- Survival and EQ-5D-5L
At visit 1 to visit 10 ( Day1- day10)
- Clinical evaluation (cardiac frequency, saturation, tracheal secretions, PaO2/FiO2 ratio, body temperature, mechanical ventilation support)
- Study drug administration (daily)
- Collection of respiratory fluid and blood for biobank (day 3 and day 7)
- Liver function test (AST, ALT, bilirubin), blood white cells count and EKG (Liver, day 3 and day 7)
- Treatment compliance
- Adverse event
- Concomitant medications (antimicrobial therapy and steriods)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ventilators-associated pneumonia (VAP) or hospital -acquired pneumonia requiring invasive ventilation (V-HAP)
- •Diagnosis of HAP according to European guidelines : association of two clinical criteria (body temperature > 38°c and purulent pulmonary secretions), the appearance of a new infiltrate or change in an existing infiltrate on chest radography, and respiratory sample (AET, BAL, mini-BAL or blind BAL) collected for bacteriological diagnosis (results can be pending at inclusion). The diagnosis of HAP can have been made outside of ICU
- •VAP : patients should have received machenical ventilation via an endotracheal or nasotracheal tube for the least 48h at the time of HAP diagnosis. V-HAP : patients should have been hospitalized for the least 48 hours before the onset of the first signs or symptoms and required invasive mechanical ventilation during HAP treatment
- •Biological systemic inflammatory response defined according to the on-site standard of acre (CPR > 125 mg/L and/or PCT > 2µg/L and/or ferritin blood level > 650 ng/mL
- •Receiving antimicrobal therapy for the current episode of HAP pneumonia for less than 72 hours
- •Informed consent from legal representative or emergency procedure (when possible according to national regulation). If it's impossible to obtain patient consent before the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible
- •Person insured under a helth insurance scheme
排除标准
- •Pregnant women (serum or urine test), breastfeeding woment
- •Patient under legal protection (inc. under guardianship or trusteesheep)
- •Hypersensitivity to baricitinib
- •Uncontrolled herpes zoster, viral hepatitis, infection with human immunodeficiency virus, fungal infections or tuberculosis
- •Severe hepatic insufficiency (child-Pugh B or C)
- •Acute or chronic renal insufficiency (modification of diet in renal disease (MDRD) creatinine clearance < 30 ml/min/1.73 m²)
- •Persistent anemia (haemoglobin < 8 g/L), lymphopenia (absolute lymphocyte < 500 cells/mm3)
- •Immunosuppression (hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion or anti-graft rejection drug)
- •Recent (<90 days) trhomboembolic event (venous trhombosis, pulmonary embolism, myocardial infarction, and/or stroke)
- •Participation to an interventional drug study within 1 month prior to the inclusion
研究组 & 干预措施
Baricitinib + Standard of care
Baricitinib injected per os for 10 days (4mg/day). the first administration of this treatment is performed within the 6 hours following the randomization, followed by daily administration for a total of 10 days.
The standard of care : for treating HAP will comply with international guidelines. For all patients, empiri antimicrobial therapy is initiated imedialty after collecting the respiratory sample and can thus be started before the randomization to avoid delayed antimicrobial therapy. Its recommanded to broaden the spectrum in case of resistant bacteria resistant to the empirical antimicrobial therapy but il is not recommanded to prolong the antibiotic tratment for more than 7-8 days
干预措施: Baricitinib 4 MG (Drug)
Standard of care alone
Same as described in arm 1
干预措施: Baricitinib 4 MG (Drug)
结局指标
主要结局
Determine the safety (phase II), of baricitinib plus standard of care (SOC) as compared to (SOC) alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile
时间窗: Day 28
Using a hierarchic procedure. We will test the baricitinib superiority on the clinical cure rate at the test-of-cure visit realized 10-12 days after randomization or at the ICU discharge. If the superiority criterion is met at the test-of-cure visit, we will test the baricitinib superiority on the rate of all-cause mortality on Day 28
Determine the efficacy (phase III) of baricitinib plus standard of care (SOC) as compared to (SOC) alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile
时间窗: Day 28
Using a hierarchic procedure. We will test the baricitinib superiority on the clinical cure rate at the test-of-cure visit realized 10-12 days after randomization or at the ICU discharge. If the superiority criterion is met at the test-of-cure visit, we will test the baricitinib superiority on the rate of all-cause mortality on Day 28
次要结局
- To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity(Month 3 and Month 6)
- To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction(Up to Month 3)
- To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction(Up to Month 3)
- To demonstrate the efficacy of baricitinib on pneumonia-associated mortality(Month 3 and Month 6)